Wound dressing including a biocelulose layer having a bacteria-adsorbing design

ABSTRACT

A wound dressing including at least one layer made of microbially produced cellulose formed into a biocellulose layer, wherein the wound dressing is configured to adsorb bacteria and wherein the thickness of the bio-cellulose layer is between 0.08 and 1.5 mm, as well as a method for producing such a wound dressing.

TECHNICAL FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a wound dressing comprising at leastone layer of microbially produced cellulose (biocellulose layer). Thewound dressing is designed such that it adsorbs bacteria. The inventionfurther relates to a method for producing such a wound dressing.

Wound dressings for healing burns, skin lesions or poorly healing woundsare known. Thus U.S. Pat. No. 4,588,400 A, U.S. Pat. No. 4,655,758 A andU.S. Pat. No. 4,788,146 A describe materials for such applications,which are produced on the basis of microbially produced cellulose. Thesedocuments also describe that the biocellulose layer can be impregnatedwith bacteriostatic agents such as silver nitrate or benzalkoniumchloride. Methods for producing biocellulose are also described in WO86/02095 A1 and WO 2004/050986 A. EP 1 356 831 A also describes theapplication of biocellulose in the treatment of wounds.

According to WO 2005/009276 A biocellulose can be provided withpolyhexamethylene biguanide hydrochloride to impart antimicrobialactivity. The corresponding wound dressings are intended to releasemoisture and are accordingly characterized by a very high water contentand a correspondingly low cellulose content. In WO 2005/009276 A wounddressings are used specifically for chronic wounds. However, for burns,excessive moisture can be contraindicated.

EP 1 438 975 A discloses a moisture-releasing amorphous hydrogel basedon microbial-derived cellulose for application to wounds.

In addition to the mentioned disadvantages of a high moisture(contraindicated for burns) the infection of the wound can be increasedby such a gel.

The product Cuticell® Epigraft from BSN medical GmbH, Hamburg, FederalRepublic of Germany, consists of a pure cellulose membrane which isformed by the microorganism Acetobacter xylinum. The product istransparent and thus allows the healing of the wound to be observedduring treatment without the wound dressing having to be destroyed. Suchbiocellulose-based wound dressings are suitable for the treatment ofsplit-skin graft donor sites, burns, skin cracks, wounds and skinlesions (such as skin abrasions, incised wounds and small surgicalwounds). However, commercially available biocellulose-based wounddressings are thin and thus delicate during application. If appliedincorrectly, contamination can easily occur. Thus infected wounds cannotbe treated with biocellulose-based wound dressings. There is thus arequirement for wound dressings which can also be used for infectedwounds as well as chronic wounds with exudate.

Bacteria-adsorbing compositions are also known. Thus EP 0 162 026 Adescribes that bacteria-adsorbing compositions can be used for treatingexternal infections, which leads to a better removal of bacteria andother microorganisms. The compositions contain a hydrophilic materialsuch as cotton which is rendered hydrophobic by treatment with forexample dialkyl carbamoyl chloride.

Moreover WO 2006/062470 A discloses a wound dressing which has, on theside facing the wound, a hydrophobic layer which binds suchmicroorganisms, above it an absorbent, hydrophilic layer, and apreferably transparent polyurethane layer as cover layer. The main taskof such products is to adsorb bacteria, i.e. the field of use of suchproducts is limited and they must always be combined with a furtherwound dressing. Such products are thus suitable particularly forshort-term wound coverage.

DE 196 31 421 A also deals with hydrophobized carrier materials whichcan adsorb bacteria. The product Cutisorb® Sorbact® from BSN medicalGmbH, Hamburg, Federal Republic of Germany, has for example a layer ofhydrophobized acetate or cotton fabric.

DE 101 35 676 A discloses that (optionally microbially produced)cellulose can be doped with chitosan, hyaluronic acid or derivatives ormixtures thereof. The doped film is used, among other things, asphysiological diaphragm, artificial bloodstream and/or a pump forinfusion or dialysis. In such applications it is impossible for proteinsto be absorbed, which is why the films according to DE 101 35 676 A donot adsorb bacteria.

BRIEF SUMMARY OF THE INVENTION

Thus the object of the present invention is to expand and improve thefield of use of wound dressings, in particular biocellulose-based wounddressings. A special wound climate which is sealed off from externalinfluences is to be created by the wound dressings according to theinvention. The nanostructure of biocellulose is well suited for theadsorption of newly formed cells.

It has now surprising been shown that this object is achieved by a wounddressing which has at least one layer of microbially formed cellulose(called biocellulose layer below), wherein the wound dressing isdesigned such that bacteria are adsorbed. The biocellulose layer has athickness of from 0.08 to 1.5 mm.

In a preferred embodiment the biocellulose layer is characterized by thefollowing parameters:

-   -   a thickness of from 0.10-0.25 mm,    -   a water vapour transmission of more than 300 g/m²*24 h,        preferably of more than 500 g/m²*24 h, in particular 1000-3000        g/m²*24 h at 38° C., and/or    -   a mass per unit area of 7 to 75 g/m², preferably 9-50 g/m², in        particular 10-40 g/m², in particular 11-22 g/m².

Advantageously the biocellulose is a biocellulose produced according toa static method. This biocellulose has an advantageous three-dimensionalmultilayer structure. In contrast, biocellulose types which are producedin a stirred-tank bioreactor according to the teaching of U.S. Pat. No.5,846,213 A1 are not preferred.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram illustrating a method for producing thewound dressings according to one embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

According to a first embodiment of the invention the wound dressing ischaracterized in that the bacteria-adsorbing design consists of thebiocellulose layer itself being designed hydrophobic. This hydrophobicdesign can be a treatment with dialkyl carbamoyl chloride and/or alkeneketene dimer as is known in the state of the art.

In preferred methods for the hydrophobic design of the biocelluloselayer such a layer has a hydrophobic design when its biocellulosecontent is greater than approximately 5 wt.-%, preferably greater than20 wt.-%, more preferably greater than 60 wt.-%, in particularpreferably greater than 80 wt.-%, such as greater than 90 wt.-%, greaterthan 95 wt.-% or even greater than 97 wt.-%, such as for example 99wt.-%.

In a second embodiment the bacteria-adsorbing design of the wounddressing consists of the wound dressing having, in addition to thebiocellulose layer, at least one hydrophobic layer on the side of thebiocellulose layer facing the wound.

This additional hydrophobic layer can contain cellulose acetate fabric,viscose fabric, cotton fabric or a mixed fabric, wherein hot-meltadhesive fibres are preferred as mixed fabric. Hydrophobic layers basedon cellulose acetate fabric and cotton fabric, in particular celluloseacetate fabric, are particularly preferred. The hydrophobizing of thehydrophobic layer can consist of a treatment with dialkyl carbamoylchloride and/or alkene ketene dimer. In a preferred embodiment thehydrophobic layer and the biocellulose layer are grown together in oneproduction process. Alternatively it is possible that there is anadhesive layer between the hydrophobic layer and the biocellulose layeror that the two layers have been joined together by a lamination method.

If the base material used for producing the hydrophobic layer isnaturally hydrophilic, as is the case for example with cellulose andviscose, this base material is treated with the help of a coating inorder to produce the hydrophobic layer.

According to a third embodiment, in the case of the wound dressingaccording to the invention the biocellulose layer is designedhydrophobic and also a hydrophobic layer is present on the side of thebiocellulose layer facing the wound.

There can also be a cover layer on the side of the biocellulose layerfacing away from the wound. However, in a preferred embodiment there isno cover layer on the side of the biocellulose layer facing away fromthe wound. Instead, the wound is bandaged normally.

The production of biocellulose by bacteria is based on the excretion ofnano-fine cellulose filaments by the bacteria. This process takes placein a controlled manner under specific climatic conditions in a nutrientsolution. It is thus a biotechnical process. The bacteria graduallyexcrete so much cellulose that a gel cushion of biocellulose forms. Byshaping or incorporation into the biocellulose gel cushion while it isstill growing, the end-product can be influenced. For example it is thuspossible to join together the additional hydrophobic layer and thebiocellulose layer by ingrowth of the bacteria during the biotechnicalproduction process.

The biocellulose can be grown such that it has open structures in orderto promote healing of the wound by direct contact on the one hand and totransport the wound liquid of the infected wound into the wound dressingon the other, wherein the wound liquid with the infectious bacteriacontained therein is adsorbed.

In all embodiments of the invention it is preferred that the wounddressing is provided with one or more antimicrobial substance(s) torender it antimicrobial. This design can consist of an impregnation ofthe biocellulose layer or of an impregnation of the biocellulose andhydrophobic layer. Alternatively the finished wound dressing can bedesigned antimicrobial in all layers contained therein.

The invention is suitable in particular for preventive application insplit-skin harvesting or for burns, in particular when these wounds arealready infected.

Split skin is suitable in particular for covering large areas, e.g.after burns, especially as the donor sites can regenerate quickly. Theremoval takes place usually on flat areas of skin, preferably on thethigh, back, bottom or stomach. In the harvesting of split skin,following subcutaneous injection of local anaesthetic, the uppermostepithelial layers are stripped with a scalpel or dermatome.

The invention also relates to a method for producing the wound dressingsaccording to the invention. In a preferred method which is shown in FIG.1, the biocellulose layer is provided in a moist state. Thebacteria-adsorbing design is achieved by calendering. The wound dressingis oven-dried immediately after calendering. FIG. 1 shows

-   -   (1) the biocellulose layer in a moist state,    -   (2) the hydrophobic layer,    -   (3) the calendering rollers and    -   (4) the oven for drying.

In a first embodiment, on the wound side the wound dressing according tothe invention comprises a (preferably open-meshed) acetate woven orcotton fabric with a mass per unit area of from 60 to 200 g/m²,preferably 80 to 150 g/m², in particular 90 to 130 g/m², such as 110g/m², provided with a microbially adhesive substance such as for exampleDAAC, joined to a top-side biocellulose layer with a mass per unit areaof from 3 to 100 g/m², preferably 5 to 80 g/m², in particular 10 to 40g/m².

In a further embodiment the wound dressing according to the inventioncomprises a cellulose-based nonwoven (viscose, cotton or as a mixturewith non-cellulose fibres) with a mass per unit area of from 5 to 120g/m², preferably 10 to 100 g/m², in particular 20 to 60 g/m², likewiseprovided with a microbially adhesive substance and a top-sidebiocellulose layer.

In a third embodiment the wound dressing according to the inventioncomprises the acetate fabric as described above which is surrounded bybiocellulose, with the result that the total mass per unit area of themicrobial cellulose, including the acetate fabric, is approximately 10to 150 g/m², preferably 20 to 120 g/m², in particular 30 to 80 g/m².

The invention claimed is:
 1. A wound dressing comprising at least onelayer of microbially produced cellulose formed into a biocelluloselayer, wherein (i) the wound dressing adsorbs bacteria, (ii) thebiocellulose layer of the wound dressing has a thickness of from 0.08 to1.5 mm, and (iii) at least one hydrophobic layer attached on a side ofthe biocellulose layer adapted to face a wound, wherein: the hydrophobiclayer is treated with dialkyl carbamoyl chloride, alkene ketene dimer,or a combination thereof, and the biocellulose layer has a water vapourtransmission rate of more than 300 g/m² per 24 h at 38° C.
 2. The wounddressing according to claim 1, wherein the biocellulose layer has athickness of from 0.10 to 0.25 mm.
 3. The wound dressing according toclaim 1, wherein the biocellulose layer has a mass per unit area of from7 to 75 g/m².
 4. The wound dressing according to claim 1, wherein thebiocellulose layer is hydrophobic.
 5. The wound dressing according toclaim 1, wherein the hydrophobic layer is cellulose acetate fabric,viscose fabric, cotton fabric or a mixed fabric.
 6. The wound dressingaccording to claim 5, wherein the mixed fabric comprises hot-meltadhesive fibres.
 7. The wound dressing according to claim 1, wherein thehydrophobic layer and the biocellulose layer are joined together byingrowth of bacteria during a biotechnical production process.
 8. Thewound dressing according to claim 1, wherein the biocellulose layer hasa water vapour transmission rate of more than 500 g/m² per 24 h.
 9. Thewound dressing according to claim 1, wherein the biocellulose layer hasa water vapour transmission rate of 1000 to 3000 g/m² per 24 h at 38° C.10. The wound dressing according to claim 1, wherein the biocelluloselayer has a mass per unit area of from 9 to 50 g/m².
 11. The wounddressing according to claim 1, wherein the biocellulose layer has a massper unit area of from 10 to 40 g/m².
 12. The wound dressing according toclaim 1, wherein the biocellulose layer has a mass per unit area of from11 to 22 g/m².